Platelet aggregation has been shown to be a consistent manifestation of endotoxin shock. It is possible that prostaglandin metabolism is altered by endotoxin as a mechanism for its effect on aggregation. Thromboxane A2, a potent aggregant, is synthesized in the platelet. In the blood vessel wall, a potent anti-aggregant, Prostaglandin I2, is formed. Both sites will be studied in order to determine the specific effect of the endotoxin molecule as well as that of endotoxemia on prostaglandin metabolism. A dose-response relationship will be established between endotoxin and platelet aggregation in dogs. Platelets from endotoxemic dogs will be studied to reveal their aggregation characteristics and prostaglandin (PG) synthesis. Platelet PGE, PGG(H) and PGF will be measured by radioimmunoassay. Synthesis of anti-aggregant PGI in endotoxemic vascular tissue will be assayed against aggregating platelets. In vitro studies will also be carried out to pharmacologically determine the site of action for endotoxin on Thromboxane synthesis in aggregating platelets and on prostaglandin I synthesis in normal vascular tissue. In order to evaluate the role of endogenous PGI in maintaining circulating platelet numbers during shock, a new dose-response curve (endotoxin -vs- platelet count) will be established using dogs in which PGI synthesis has been blocked by 15-hydroperoxyarachidonic acid.